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27 Cards in this Set

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Pyruvate Dehydrongenase Rxn
Overall pyruvate is OXIDATIVELY DECARBOXYLATED to form an Acetyl CoA and CO2
Same overall rxn as the α-ketoglutarate dehydrongenae in TCA
PDH complex Five Enzymes
Pyruvate Dehydrogenase E1
Dihydrolipoyl Transacetylase E2
Dihydrolipoyl Dehydrongenase E3
PDH Kinase E4
PDH Phosphatase E5
PDH complex Five Cofactors
Thiamine Pyrophosphate
Lipoic Acid
Coenzyme A
FAD+
NAD+
E1
Assists in attaching Pyrucate to TPP (Vit. B)
Catalyzes decarboxylation of pyruvate
E2
Transfers remaining acetyl group (after pyruvate was decarboxylated) from TPP to LIPOAMIDE
Catalyzes the transfer of Acetyl group to Coenzyme A (cofactor) to form Acetyl CoA
E3
Catalyzes the reoxiation of the reduced LIPOAMIDE in order for process to continue
Electrons then transdferd to FAD (cofactor) to form FADH2, then e- transdferd to NAD+ to form NADH
Catalyzes Transfer of Electrons to NAD+ (co-factor)
Coenzyme A (CoA)
Contains free (-SH) group
Group can react with a carboxyl group to form a thiol-ester
Pantothenate (Vit. B5)
Essesential food factor which forms part of CoA
Thiol-Ester Groups
Involved in many transfer reactions involvng acyl groups including:
acetyl- and fatty acyl- groups
Regulation of PDH
Product Inhibition
Products of PDH, AcetylCoA and NADH inhibit PDH in a compettive fashion as feedback inhibitors
What is the E1 compenent of PDH regulated by?
Regulated by covalent modification (phosphorylation/dephosphorylation)
Regulation of PDH
Covalent Modification
PDH Kinase
Phosphorylates and INACTIVATES the complex by adding a Pi
Regulation of PDH
Covalent Modification
PDH Phosphatase
Dephosphorylates and ACTIVATES the complex by taking away a Pi
Allosteric Regulation of PDH by Acetyl CoA and NADH
Acetyl CoA and NADH not only inhibit PDH activity as competitive inhibitors, but also activate PDH KINASE activity which will lead to PDH phorphrylation (inactivation)
What substrates enhance PDH activity by inhibing PDH kinase activity?
Pyruvate, CoASH, NAD and AMP
What electrolytes enhance PDH activity?
Both Mg+ and Ca2+ by stimulating PDH phosphatase activity
What is α-ketoglutarate dehydrogenase complex also know as?
TCA Cycle
What makes α-ketoglutarate dehydrogenase different from PDH complex different?
Does NOT have its own kinase and phosphatase
Therefore it catalyzes a similar rxn but the regulation is different
What are some symptoms of PDH deficiency?
Elevated serum levels of pyruvate, lactae and alanine
Chronic Lactic Acidosis
Severe neurological defects
What are some remedies of PDH deficiency?
Diet with REDUCED carbohydrates
Dichloroacetate, and INHIBITOR of PDH kinase
What does the PPP pathway mainly create and what catalyzes it?
Main production of NADPH
Catalized by two enzyes:
G6PD and 6-Phosphogluconate dehydrogenase
What is NADPH important for?
FA synthesis, glutathione reduction and other anabolisms
What does glutathione do?
Helps protect cells against oxidative stress
What will reseult in G6PD defeciency?
Imbalence between NADPH and NADP+.
Lower NADPH will in turn affect Glutathione
Erythrocytes are most sensitive and mutations could result in hemolytic anemia
Defciencies of what will affect both PDH and α-ketoglutarate dehydrogenase?
Thiamine (B1)
Riboflavin (B2)
Niacin (B3)
Pantothenic Acid (B5)
Lipomide
How does NADPH regulate PPP?
Is a strong inhibitor of G6PD
Lower NADPH will enhance PPP and NADPH generation and vice versa
What induces synthessis of G6PD?
Induced by increase insulin/glucagon ratios after high carb meal